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Circadian metabolomics from mice and men: Insights for mechanism and medicine
Published on Jul 21, 20142187 Views
A biological "circadian" clock regulates nearly all aspects of mammalian physiology in accordance with the solar day. Not only sleep and wake, but also mood and cognition, circulation and cardiac fun
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Circadian metabolomics from mice and men: insights for mechanism and medicine00:00
Mammalian physiology is circadian00:17
Mammalian physiology is circadian00:33
How do these clocks affect metabolism, and in particular metabolomics?00:47
Ten percent of mouse genes are expressed in circadian fashion01:10
20% of mouse liver proteins are rhythmic01:32
And not surprisingly, 20% of the mouse metabolome is also rhythmic…02:03
Overall results03:04
Rhythmic plasma metabolites03:29
Rhythmic saliva metabolites03:31
Rhythmic saliva metabolites03:43
Rhythmic saliva metabolites03:50
The next step: Metabolic breathylomics directly in the clinic03:56
Human circadian breath metabolome from 3 subjects04:32
Human circadian breath metabolome from 3 subjects04:59
Human circadian breath metabolome from 3 subjects05:08
Supervised PCA of Breath Metabolome of One Subject during 24 hours05:10
Breathprint predicts time of day ±3hrs05:26
Why is circadian time relevant to medicine?05:40
Set-up for mouse breath analysis06:26
PK curve for ket and metabolites06:56
Dose response for ket and nk07:13
Circadian modulation of ket metabolites07:24
A current challenge in medicine: identifying when timing matters07:54
Circadian behavior predicts chemotherapy survival in humans.08:15
Methods: measuring cellular clocks08:42
Clock in glioblastoma cell lines09:44
Clock in glioblastoma cell lines10:03
Clock in glioblastoma cell lines10:13
Clock in glioblastoma cell lines10:15
Clocks in GBM10:39
Are these differences relevant for cancer progression?11:22
Killing the clock in a cancer cell line11:55
Breaking the clock in C26 in 2 ways12:18
Breaking the clock in C26 in 2 ways13:36
Hypothesis: maybe clock function is being systemically driven here13:53
In vivo luminometry- principle14:34
Rhythmic tumor: Bmal-luciferase in vivo15:09
Arrhythmic tumor: Bmal-luciferase in vivo15:53
Conclusions: A four-clock problem?16:30
Thank you17:52